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...................... associated with a 3035% reduction in the risk of recurrence compared with placebo (Supplementary Data Table 15).355,356 However, more recently, another trial demonstrated the superiority of anticoagulation with rivaroxaban, either 20 or 10 mg o.d., over aspirin for secondary prophylaxis of VTE recurrence.352

A randomized, placebo controlled study evaluated sulodexide (2  250 lipasemic unit capsules b.i.d.) for the prevention of recurrence in 615 patients with a first VTE event without an identifiable risk factor, who had completed 312 months of oral anticoagulant treatment (Supplementary Data Table 15).357 Sulodexide reduced the risk of recurrence by 50% with no apparent increase in bleeding events. However, only 8% of patients in this study had PE as the index VTE event.357

8.4 Recommendations for the regimen and duration of anticoagulation after pulmonary embolism in patients without cancer

Recommendations Classa Levelb Therapeutic anticoagulation for >_ 3 months is recommended for all patients with PE.347 I A Patients in whom discontinuation of anticoagulation after 3 months is recommended For patients with first PE/VTE secondary to a major transient/reversible risk factor, discontinuation of therapeutic oral anticoagulation is recommended after 3 months.331,340,341 I B Patients in whom extension of anticoagulation beyond 3 months is recommended Oral anticoagulant treatment of indefinite duration is recommended for patients presenting with recurrent VTE (that is, with at least one previous episode of PE or DVT) not related to a major transient or reversible risk factor.358 I B Oral anticoagulant treatment with a VKA for an indefinite period is recommended for patients with antiphospholipid antibody syndrome.359 I B Patients in whom extension of anticoagulation beyond 3 months should be consideredc,d Extended oral anticoagulation of indefinite duration should be considered for patients with a first episode of PE and no identifiable risk factor.330,331,347,351353 IIa A Extended oral anticoagulation of indefinite duration should be considered for patients with a first episode of PE associated with a persistent risk factor other than antiphospholipid antibody syndrome.330,352,353 IIa C Extended oral anticoagulation of indefinite duration should be considered for patients with a first episode of PE associated with a minor transient or reversible risk factor.330,331,352 IIa C NOAC dose in extended anticoagulatione If extended oral anticoagulation is decided after PE in a patient without cancer, a reduced dose of the NOACs apixaban (2.5 mg b.i.d.) or rivaroxaban (10 mg o.d.) should be considered after 6 months of therapeutic anticoagulation.352,353 IIa A Extended treatment with alternative antithrombotic agents In patients who refuse to take or are unable to tolerate any form of oral anticoagulants, aspirin or sulodexide may be considered for extended VTE prophylaxis.355357 IIb B Follow-up of the patient under anticoagulation In patients who receive extended anticoagulation, it is recommended that their drug tolerance and adherence, hepatic and renalf function, and bleeding risk be reassessed at regular intervals.259 I C

b.i.d. = bis in die (twice a day); DVT = deep vein thrombosis; NOAC(s) = non-vitamin K antagonist oral anticoagulant(s); o.d. = omni die (once a day); PE = pulmonary embolism; VKA = vitamin K antagonist; VTE = venous thromboembolism. aClass of recommendation. bLevel of evidence. cThe patient’s bleeding risk should be assessed (see Supplementary Data Table 14 for prediction models) to identify and treat modifiable bleeding risk factors, and it may influence decision-making on the duration and regimen/dose of anticoagulant treatment. dRefer to Supplementary Data Table 9 for therapeutic decisions in specific clinical situations. eIf dabigatran or edoxaban is chosen for extended anticoagulation after PE, the dose should remain unchanged, as reduced-dose regimens were not investigated in dedicated extension trials.313,350 fEspecially for patients receiving NOACs. Downloaded from academic.oup.com/eurheartj/article/41/4/543/5556136 by guest on 07 October 2026